The purpose of this investigation is to confirm the presence of an HLA marker for susceptibility to melanoma, and to determine if there is a relationship to stage of disease and/or survival as well as provide evidence that a gene for susceptiblity to melanoma exists in the population of white patients seen at the Melanoma Clinic of UAB. Preliminary studies revealed a significant association of HLA-DR4 (p less than 0.0026) with melanoma in this population. There was a high frequency of individuals with blonde to light hair (41%). Moreover, 13% of the probands reported melanoma in their first degree relatives. The proposed study will attempt to confirm this observation by critically matching the patients and controls with regard to skin color by use of skin reflectance. In addition, other genetic markers to include properdin factor B (Bf), complement components C2 and C4, glyoxylase (GLO) group-specific component (Gc), and Gm allotypes will be analyzed for association with melanoma. The study will also attempt to determine if (1) there are different genetic associations for each of the three stages of melanoma at initial presentation; (2) if the above genetic polymorphisms can be used to identify which patients are at risk for advancing from Stage I to Stage II or III disease; and (3) if the genetic markers can be used alone or with other prognostic factors to predict probability of surviving melanoma. Based on preliminary data which revealed that 13% of the probands identified reported melanoma in their first degree relatives, a specific aim will also be to determine a major gene model for susceptibility to the disease by conducting a segregation analysis on families ascertained through a melanoma proband. Use will be made of UAB's Melanoma Registry for this aspect of the study. Lastly, an attempt will be made to map the melanoma susceptiblity gene by using the parameter estimates and best fitting major locus model determined from the segregation analysis. This will involve a genetic linkage analysis on extended families with two or more members affected with melanoma that have been typed for the various markers coded by genes at the major histocompatibility complex (HLA, Bf, C2, C4 and GLO). These studies should provide additional information with regard to the role of genes in the onset of melanoma as well as survival once the disease has occurred.